The purpose of this grant is to characterize T helper cells which have specificity for idiotype, allotype or isotype. The studies are based on our finding that the normal response to sheep red blood cells (SRBC) is dependent on the function of T helper cells restricted to helping B cells of a particular immunoglobulin heavy chain haplotype (lgh). This restriction does not depend on the genotype of the helping T cell but rather on that of the B cells present at the time of antigen priming. The studies make use of mouse strains congenic for lgh alleles, nude, and xid (x-linked immune deficiency) that we have developed. Helper cells with carrier (THcar) and immunoglobulin (THlg) specificity will be raised in separate mice and be tested for their ability to act synergistically in vivo. The Lyt, la and Qa surface antigens of the THig population will be determined. An in vitro assay for THig will be developed. The mechanism of THig priming will be tested using free antibody, antigen-antibody complexes and antigen activated B cells to induce T help. The VH or CH specificity of the help generated will be investigated using VH-CH recombinant mice. The possible restriction of THig generation or expression will be examined using H-2 and Igh congenic mice in cell transfer experiments and in vitro. The role of B cell subpopulations in generating or responding to THig help will be tested for by the use of selective deletion and enrichment techniques (panning) for Mu, Gamma 2a, and Alpha-bearing cells. Long term cultures will be established using interleukin ll and stimulating igh containing products. Attempts will be made to identify cells with THig capabilities. Once identified, we will try to clone the THig cells for future detailed studies.